Anderson D, Hughes J A, Nizankowska E, Graca B, Cebulska-Wasilewska A, Wierzewska A, Kasper E
BIBRA International, Surrey, United Kingdom.
Environ Mol Mutagen. 1997;30(2):205-16. doi: 10.1002/(sici)1098-2280(1997)30:2<205::aid-em13>3.0.co;2-h.
The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.
本交流的目的是确定肺癌患者和健康供体中癌症与细胞遗传学损伤生物标志物及ras p21癌蛋白水平之间是否可能存在关联,以及各种外源性混杂因素(如吸烟习惯)和内源性因素(年龄、性别等)是否会影响这些生物标志物。从31例肺癌患者治疗前及35例社会经济地位相似且来自波兰同一地区的健康供体采集外周血和血浆。检测血液中的染色体畸变(CA)、姐妹染色单体交换(SCE)、高频细胞(HFC)和增殖率指数(PRI)以及血浆中的ras p21癌蛋白。这些参数被用作遗传毒性异常的生物标志物。检测所有生物标志物与年龄、性别、吸烟习惯和直系家族癌症病史等混杂因素之间的关系。通过t检验、方差分析(ANOVA)和逐步多元回归分析对结果进行分析。癌症患者中所有类型的CA(包括和不包括裂隙)、异常细胞百分比、SCE和ras p21癌蛋白在统计学上均显著高于健康供体。尽管癌症患者组中年龄较大的女性人数少于男性,但性别存在差异,女性的CA、SCE和HFC在统计学上显著增加,而ras p21癌蛋白没有增加。细胞遗传学损伤与各组直系家族中的其他癌症无关。癌症患者组中吸烟者和非吸烟者的所有主要CA参数差异显著,健康供体组中SCE和HFC存在差异。这些参数也随吸烟数量和吸烟年限显示出显著变化。多元回归分析显示细胞遗传学损伤、ras p21癌蛋白与癌症之间存在显著关联。总之,本研究中的细胞遗传学损伤和ras p21癌蛋白似乎是与癌症相关的生物标志物,但尚未得到因果关系的证明,年龄、性别和吸烟等混杂因素可能会对它们产生影响。